The overall goal of this P01 application is to continue address of the hypothesis that antigen presenting cells (dendritic cells, macrophage/monocytes), through their interaction with components of the cellular immune system (NK T-cells, regulatory T cells), form a critical facet for the immune dysregulation which results in type 1 diabetes. This P01 renewal will examine this hypothesis with three separate but highly interactive Projects and will be supported by two well-established Core facilities (A-Administration;B-Pathology & Immunology). The Program requires an effective Administrative Core component as a central element of fiscal and scientific coordination. The four goals of Core A are as follows: 1) To coordinate the budgetary and fiscal aspects of the Program. The proposed Program involves direct cost disbursements to investigators of the three Projects and two Cores;hence careful oversight represents an absolute administrative requirement. 2) To facilitate communication among investigators within the Program. This will take form through performance of many functions ranging from regularly scheduled meetings between Program investigators to training of Project Investigators by Program Cores. 3) To coordinate the goals and activities of the PO1 as a Program Executive Committee and respond to input provided by an External Advisory Committee, both for the purpose of maximizing the progress and success of the Program: These committees will meet on a regularly scheduled basis and provide counsel to the Program Investigators regarding their program and recommendations for improvement. 4) To organize the collection of human materials, generate appropriate data sets, provide statistical support to the Program, assure compliance with appropriate regulatory bodies and edicts (e.g., IRB, IACUC, Health Insurance Portability and Accountability Act, etc.) and facilitate communication of Program results. In addition to the aforementioned functions, the administrative staff of the Program will also be responsible for communication with the NIH staff, for assistance with publications and presentation of Program results. The successful completion of these P01 studies should prove beneficial to improving our understanding of those events critical to the pathogenesis and natural history of type 1 diabetes, identifying markers that enhance our ability to monitor cellular immune activities in the disease, and developing immunotherapies capable of preventing or reversing the disorder.